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Abstract: Karanjin (1) is a natural furanoflavonol derivative isolated from seeds of Pongamia pinnata (L.) Pierre. In this paper, we have accomplished a concise total synthesis of karanjin (1) as well as its natural analogues pongapinnol D (2), 3-hydroxy-6-methoxy-2-phenyl-4H-furo[2,3-h]-1-benzopyran- 4-one (3) and 3,6-dimethoxy-2-phenyl-4H-furo[2,3-h]chromen-4-one (4). One-pot aerobic oxidation was the key step to afford the flavonol framework under mild conditions. The anti-inflammatory properties of synthesized 1–4 were determined against NO production in the LPS-stimulated RAW264.7 cells.

Voltage/Frequency Islands (VFIs) are practically used in multicore systems. VFIs cluster cores that share the same Voltage/Frequency (V/F) level for the entire application runtime. Using VFIs, switching V/F levels has less overhead per-core while saving more energy in exchange for tolerable execution delay. This paper targets the well-known K-means algorithm for clustering cores, where each cluster contains cores with similar computational workloads across applications phases. K-means produces sub-optimal clusters when cores workloads do not have the same variation across all phases. Furthermore, the workload variations require running a VFI with a different V/F level per-phase. This paper presents a fast heuristic that facilitates clustering by sorting computational workloads per-phase before applying K-means. The VFIs V/F levels are dynamically adjusted to meet energy budget constraints. This framework provides a guideline for users to choose a number of clusters that satisfies system configurations and energy efficiency preferences. Three parameters are evaluated to represent the computational workloads: utilization, Instruction-Per-Cycle (IPC), and execution time. For an application with highly varying workload, execution time achieves 52 and 65% more energy efficiency compared to utilization and IPC, respectively. Results show that the degree of workload variations for different applications impacts changing or fixing VFIs V/F levels.

Millpuline B (1), isolated from Millettia pulchra, is a naturally occurring bioactive compound with a chiral center. Herein, we report the first total syntheses of both (+/-)-Millpuline B from comm...

Syringin (1), a natural bioactive glucoside isolated from the root of Acanthopanax senticosus (Rupr. Maxim.) Harms, possesses significant anti-inflammatory activity. In this study, we have accomplished the total syntheses of syringin (1), along with its natural analogues 2-12, from a common starting material, syringaldehyde (13), in 4-8 steps with an overall yields of 11.8-61.3%. The anti-inflammatory activities of these compounds were determined against NO production in the LPS-stimulated RAW264.7 cells. Among them, compounds 1-5, 7, and 9 exhibited different levels of anti-inflammatory activity.

Objective To investigate the clinical efficacy and safety of bronchial thermoplasty (BT) in treating chronic obstructive pulmonary disease (COPD) patients. Methods Clinical data of 57 COPD patients were randomized into control (n = 29, conventional inhalation drug) or observation group (n = 28, convention inhalation drug plus BT). Primary outcomes were differences in clinical symptom changes, pulmonary function-related indicators, 6-min walk test (6MWT), COPD assessment test (CAT) score, Modified Medical Research Council (mMRC) and acute exacerbation incidence from baseline to average of 3 and 12 months. Safety was assessed by adverse events. Results FVC, FEV1 and FEV1% predicted value in both groups improved to varying degrees post-treatment compared with those pre-treatment (P

Neocyclomorusin (

We consider a class of structured nonsmooth difference-of-convex minimization. We allow nonsmoothness in both the convex and concave components in the objective function, with a finite max structure in the concave part. Our focus is on algorithms that compute a (weak or standard) d(irectional)-stationary point as advocated in a recent work of Pang et al. (Math Oper Res 42:95–118, 2017). Our linear convergence results are based on direct generalizations of the assumptions of error bounds and separation of isocost surfaces proposed in the seminal work of Luo and Tseng (Ann Oper Res 46–47:157–178, 1993), as well as one additional assumption of locally linear regularity regarding the intersection of certain stationary sets and dominance regions. An interesting by-product is to present a sharper characterization of the limit set of the basic algorithm proposed by Pang et al., which fits between d-stationarity and global optimality. We also discuss sufficient conditions under which these assumptions hold. Finally, we provide several realistic and nontrivial statistical learning models where all assumptions hold.

Summary Background & Aims The rise in the prevalence of childhood obesity has increased the demand for accurately evaluating body fatness in pediatric population. The aim of this study was to provide a series of sex- and age-specific body fat reference centiles for evaluating total body fat development and fat distribution in Chinese children and adolescents using dual-energy x-ray absorptiometry (DXA). Methods A nationwide sample of Chinese children and adolescents aged 3-18 years (n=12,790) was drawn from a cross-sectional survey of the China Child and Adolescent Cardiovascular Health study (2013-2019). Fat measurements, including total fat mass index (FMI), total body fat percentage (BF%), regional FMI, trunk to leg (T/L) fat ratio and android to gynoid (A/G) fat ratio, were derived from whole body DXA scans. Sex- and age-specific centiles were estimated using the lambda-mu-sigma method and then compared with values derived from the US National Health and Nutrition Examination Survey (1999-2004) and Korean National Health and Nutrition Examination Survey (2008-2011). Results During early childhood, almost all body fat parameters decreased with age, except an increase in A/G ratio. After 7 years onward, drastic upward trends of total FMI and BF% were exhibited in boys till 10 years, followed by opposite downward trends during 11-14 years; while sustained increase of FMI was shown in girls across ages accompanied by relatively constant BF% levels. Meanwhile, steady increases were noticed for A/G ratio and T/L ratio, which were more pronounced in boys. In addition, the proposed body fat references were much lower than the US but similar to Koreans despite of subtle differences. Conclusions This is the first study to present a set of DXA-based body fat reference for Chinese children and adolescents aged 3-18 years. The new reference provides clinicians and researchers a useful tool for assessing body fat development and distribution patterns across the periods from early childhood to adolescence.

Importance Several methods have been established in recent decades that allow use of spot urine to estimate dietary sodium intake. However, their accuracies have been controversial in children. Objective To validate the performance of three commonly used methods—the Kawasaki, Tanaka, and International Cooperative Study on Salt, Other Factors, and Blood Pressure (INTERSALT) methods. Additionally, this study explored the accuracies of the Tanaka and INTERSALT methods by using spot urine samples taken at four separate times. Method Forty‐one adolescents aged 14 to 16 years completed two non‐consecutive 24‐hour urine collections and their mean values were used as reference data. The second‐morning urine was used for assessment with the Kawasaki method; a casual spot urine and spot urine samples taken at four separate times (morning, afternoon, evening, and overnight) were used for assessment with the Tanaka and INTERSALT methods. Results The mean differences were 1801 mg, 542 mg, 47 mg, and −31 mg for the Kawasaki, Tanaka, INTERSALT1 (with potassium), and INTERSALT2 (without potassium) methods with their required spot urine, respectively. The proportions of relative difference levels within ± 10% were 4.9% for the Kawasaki method, 19.5% for the Tanaka method, 36.6% for the INTERSALT1 method, and 36.6% for the INTERSALT2 method. Interpretation The INTERSALT method seemed to provide minimally biased estimations of mean population sodium intake with casual spot urine. However, there is a need to be cautious regarding inconsistencies in estimation among different levels of sodium intake. The methods assessed in this study were unable to accurately estimate sodium intake at the individual level., The INTERSALT provided unbiased estimations of mean population sodium intake in adolescents aged 14 to 16 years.

The efficient total syntheses of four biologically interesting natural glucosides Ethylconiferin, Butylconiferin, 2’-Butoxyethylconiferin and Balajaponin B, have been achieved for the first time starting from commercially available Vanilline via concise reaction sequence of 8–10 steps with the overall yield of 26–41%. This work definitely laid the foundation for the further pharmacological study of this kind of natural compounds. Meanwhile, currently developed approach could be used as a general synthetic strategy for the syntheses of other monolignol glucosides and their derivatives, and provides an opportunity for further study of the structure-activity relationship of this kind of glucosides.

Tao Wang,1,2,* Fa Long,1,* Zhihui Huang,1 Liang Long,1 Wenting Huang,1 Siyu Hu,1 Fengbo Hu,1 Peng Fu,1 Jingfan Gan,1 Hongbo Dong,1 Guomei Yan1 1University of Chinese Academy of Sciences Shenzhen Hospital, Shenzhen, People’s Republic of China; 2The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fa Long, University of Chinese Academy of Sciences Shenzhen Hospital, No. 4253, Songbai Road, Guangming District, Shenzhen, 518106, People’s Republic of China, Tel +86-755-27461986, Email longfa_923@163.comObjective: To investigate the relation of activation site and number with clinical response to bronchial thermoplasty (BT) in refractory asthma patients.Methods: This work included 106 consecutive refractory asthma patients completing three BT sessions in our hospital from May 2016 to May 2019. Procedure details included recording delivery sites and those in BT. Asthma Control Questionnaire (ACQ) scores and spirometric measurements were recorded 1-day before treatment and 6 months post-treatment to explore the effects of BT activation number and site on clinical response.Results: ACQ score (3.19± 1.14 vs 1.26± 0.63), forced expiratory volume in 1 sec (FEV1)% predicted (55.53± 21.66 vs 66.19± 22.50), FEV1 (1.53± 0.74 vs 1.93± 0.82), and forced vital capacity (FVC) (2.49± 0.86 vs 2.92± 0.94) significantly increased after three BT sessions compared with pre-session. Major bronchial ablation did not significantly improve BT response in asthma patients. Multivariate logistic regression identified baseline ACQ score and baseline FEV1% predicted as independent factors affecting the clinical response to BT. Correlation and regression analysis revealed a significant linear relationship between baseline ACQ and ACQ improvement, as well as a linear relationship between the third session activation number and ACQ improvement. Based on subgroup analysis of activation number, cohort C (activations ≥ 200) had better lung function, lower non-responding rate, and better long-term effectiveness than the other two cohorts. The activation number in the third BT session showed the strongest predictive ability compared with the first two sessions.Conclusion: Main bronchial ablation did not markedly affect clinical response to BT. Baseline ACQ and baseline FEV1% predicted were independent factors affecting clinical response to BT. Increasing the activation number might promote the therapeutic efficacy of BT, and the activation number in the third BT session correlated with and predicted the BT response.Keywords: refractory asthma, bronchial thermoplasty, activation, response, correlation

Dual-energy X-ray absorptiometry (DXA) and air displacement plethysmography (ADP) are two widely used methods for body composition analysis (BCA). However, little is known about the discrepancies in the results of BCA obtained from the two methods in Chinese population. This study aimed to compare the measurement differences between DXA and ADP in young and middle-aged Chinese adults, and to explore the influential factors of this difference.A total of 186 healthy volunteers (51.1% males) who aged 18-56 years old with body mass index (BMI) of 15.9-35.9 kg/mIn general, all the BCA measures of DXA and ADP were highly correlated (intraclass correlation coefficient ICC0.80, P 0.001), while differences were found between the two methods (all P 0.001). At the population level, greater body fat estimates (FM: 1.8 ± 3.1 kg in males and 2.2 ± 2.4 kg in females; FMP: 2.4 ± 4.2% in males and 3.1 ± 3.5% in females), whereas lower FFM (-0.2 ± 3.1 kg in males and -0.9 ± 2.4 kg in females) were found for DXA than ADP. Moreover, the average difference in FM and FMP as referred to ADP changed from positive in underweight group to negative in obesity group, and vice versa for FFM. At the individual level, the proportion of relative errors for FM and FMP within ±15% was less than 10% in underweight subjects and over 75% in those with obesity. For FFM, all underweight subjects had a relative error within 15%, and the proportion was 90.5% for obese males and 85.0% for obese females.BCA results by DXA and ADP were highly correlated, but the differences between the two methods were strongly influenced by BMI status at both population and individual levels. Caution should be especially taken when interchanging body fat results measured by the two methods in underweight and obese subjects.

MicroRNAs are emerging as important endogenous regulators of gene function and they are playing an important role in the occurrence and development of cancer. They are also regarded as robust biomarkers of cancer diagnosis and prognosis. Hepatocellular carcinoma (HCC) is a common and complex human malignancy with high mortality and morbidity in the world. MicroRNA-122 (miR-122) is a liver-specific microRNA and is closely associated with HCC metastasis, which makes miR-122 a promising target for drug design and development. In this study, we performed a cell-based screening method for discovering miR-122 activators and found that oleanolic acid (OA), a natural pentacyclic triterpene, specifically increased miR-122 expression in a concentration-dependent manner. Two HCC cell lines (HepG2 and Sk-hep-1 cells) were used to evaluate the effect of OA on cell migration and invasion abilities. The results indicated that OA attenuated the migration and invasion abilities of HCC cells by upregulating miR-122 expression. In addition, OA increased the expression of E-cadherin and decreased the expression of β-catenin, N-cadherin and vimentin. After knocking down miR-122 with miR-122 inhibitor, we found that the effect of OA on these epithelial-to-mesenchymal transition (EMT) related molecules was significantly weakened, indicating OA exhibited anti-EMT effect by increasing the expression of miR-122. These finding may help to better understand the molecular mechanism of OA's anti-metastasis activity.

Objective This study aims to evaluate the prevalence of hypertension and hypertension subtypes among Chinese children aged 6--17 years in a multicenter school-based sample by three separate screenings. Methods Students from six major cities in China (Changchun, Beijing, Jinan, Shanghai, Chongqing, and Chengdu) were recruited in this cross-sectional survey during 2012 and 2015. Each participant was seated and had three consecutive blood pressure measurements on the right arm in the morning by an automated oscillometric device and the hypertensive ones were followed to the next visit. Hypertension was diagnosed by BP references for Chinese children and adolescents in 2010. Results Data from 44 396 children aged 6--17 years were included in analysis, 50.9% of whom were boys. The prevalence of confirmed hypertension after three separate screenings was 4% in the total population, 5% in boys, and 3% in girls, respectively. The prevalence of confirmed isolated systolic hypertension (ISH), isolated diastolic hypertension (IDH), and systolic and diastolic hypertension (SDH) in the total population was 2.7, 0.3 and 1%, respectively. Conclusion Around 4% urban Chinese children and adolescents aged 6-17 years were hypertensive after three separate BP screenings in 2012-2015. ISH was the most frequent form of hypertension in children.

The purpose of this study was to explore the specific role and potential mechanism of long non-coding RNA HOTTIP in the progression of oral cancer.HOTTIP in oral cancer tissues and adjacent normal tissues was measured by quantitative real-time polymerase chain reaction (qRT- PCR) technology. After knockdown of HOTTIP expression in oral cancer cell lines, Cell Counting Kit (CCK-8), scratch healing experiment, and Transwell assay were carried out to explore cell proliferation and migration capacity. Furthermore, in order to discover the underlying mechanism, a dual luciferase experiment was designed to verify the binding of HOTTIP to the downstream miR-206 based on the prediction results of the bioinformatics prediction website. Finally, we designed a cell function recovery experiment using co-transfection technology to further confirm the regulation of HOTTIP on miR-206.HOTTIP was abnormally increased in oral cancer. At the same time, the survival analysis showed that the higher expression of HOTTIP was significantly correlated with a shorter overall survival. The results of cell functional experiments found that HOTTIP played a role in promoting tumor proliferation and migration in oral cancer cells. Besides, when HOTTIP was knocked down in oral cancer cell lines, miR-206-206 was remarkably up-regulated. Dual-luciferase reporter gene experiment confirmed the binding relationship between miR-206 and HOTTIP. In addition, miR-206 was found to be differently expressed in oral cancer tissues from that in normal control tissues. Cellular function experiments verified that HOTTIP could promote tumor proliferation activity and migration by altering miR-206 in oral cancer.HOTTIP promotes the tumor proliferation activity and migration of oral cancer cells through modulating miR-206.

Objective To investigate the associations of fat mass in specific regions with cardiometabolic risk factors in Chinese children and adolescents. Patients and Methods This cross-sectional study consisted of 8460 children and adolescents aged 6 to 18 years from Chinese urban areas who underwent dual-energy x-ray absorptiometry for regional fat masses and had cardiometabolic risk factors measured between January 1, 2013, and December 31, 2015. Results In the multivariate model containing arm fat mass, leg fat mass, and trunk fat mass, after adjustment for region, family income, age, puberty development, physical activity, and smoking, higher trunk fat mass was independently associated with greater odds of clustered cardiometabolic risk (odds ratio [OR], 2.21; 95% CI, 1.80-2.72), higher leg fat mass was associated with lower odds of clustered risk (OR, 0.72; 95% CI, 0.59-0.87), and arm fat mass was not significantly associated with clustered risk (OR, 1.22; 95% CI, 0.97-1.55). In the multivariate model including android fat mass, gynoid fat mass, and other covariates, higher android fat mass was positively associated with clustered risk (OR, 2.23; 95% CI, 1.88-2.64), but gynoid fat mass was not associated with clustered risk (OR, 0.86; 95% CI, 0.72-1.03). Analyses for individual risk factors demonstrated similar results. Conclusion Fat stored in different regions has differential influences on cardiometabolic risk in youth. Prospective studies are warranted to evaluate the long-term impacts of regional fat masses in childhood on cardiovascular risk in adulthood.

In addition to sparsity, practitioners of statistics and machine learning often wish to promote additional structures in their variable selection process to incorporate prior knowledge. Borrowing the modeling power of linear systems with binary variables, many of such structures can be faithfully modeled by affine sparsity constraints (ASC). In this note we study conditions under which an ASC system can be represented by sets in integer programs and mathematical programs with complementarity conditions (MPCC). Results of this note facilitate developing nonconvex optimization methods for variable selection with structured sparsity.

In this paper, we study the ratio of the $L_1 $ and $L_2 $ norms, denoted as $L_1/L_2$, to promote sparsity. Due to the nonconvexity and nonlinearity, there has been little attention to this scale-...

Polymorphic crystalline structure has been a key factor determining the mechanical property and degradation behavior of biodegradable polymers. Herein, we report on the polymorphic crystalline structure, phase transition, and their effects on the mechanical property and degradation behavior of poly(p-dioxanone) (PPDO), a typical biodegradable and bioabsorbable semicrystalline polymer for biomedical applications. Both the polymorphic crystalline structure and crystallization kinetics of PPDO depend on crystallization temperature (Tc) drastically. Melting enthalpy and degree of crystallinity of PPDO first decrease and then increase with increasing Tc. PPDO forms a new mesomorphic polymorph (denoted as the α′-form) during crystallization at low Tc (≤10 °C), in contrast to the common α crystals generated at high Tc (≥60 °C). The α′ crystals have weaker interchain interactions and a shorter long period than the common α crystals, indicating the looser chain packing of α′ crystals. The α′ crystals are metastabl...

Additional file of Identification of a variant form of tyrosine phosphatase LYP

Authors’ original file for figure 2

Authors’ original file for figure 1